What are the next steps in managing a patient with C3 (Complement Component 3) glomerulopathy who does not respond to treatment?

From the Guidelines

For a patient with C3 glomerulopathy who does not respond to initial treatment, the next steps should prioritize a comprehensive re-evaluation of the disease process and consideration of alternative therapeutic strategies, including participation in a clinical trial when feasible 1.

Key Considerations

• A careful assessment of the patient's current clinical status, including renal function, proteinuria levels, and any signs of disease progression, is essential.
• Consideration should be given to initiating or adjusting immunosuppressive therapy, such as adding or switching to medications like rituximab or eculizumab, which may be beneficial in some cases 1.
• Optimizing supportive care measures, including strict blood pressure control (targeting a blood pressure of less than 130/80 mmHg) and use of renin-angiotensin-aldosterone system inhibitors (such as lisinopril or losartan) to reduce proteinuria, is crucial.

Novel Therapeutic Approaches

• Given the paucity of evidence to treat C3 glomerulopathy, consideration of novel therapeutic approaches, including medications that block the alternative pathway at specific sites, may be necessary 1.
• Regular monitoring of renal function, electrolytes, and the patient's overall clinical condition is necessary to adjust the treatment plan as needed and to promptly address any potential complications.

Specialist Guidance

• In cases where the disease is progressing despite these measures, consideration of more intensive immunosuppressive regimens or novel therapeutic approaches under the guidance of a nephrologist or a specialist in glomerular diseases is recommended.

From the Research

Next Steps in Managing C3 Glomerulopathy

In patients with C3 glomerulopathy who do not respond to treatment, the following steps can be considered:

• Re-evaluation of the patient's complement profile to identify potential underlying causes of the disease 2
• Consideration of alternative treatment options, such as complement-targeting therapy with eculizumab, especially in refractory cases 3, 4
• Use of plasma therapy and immunosuppression, as shown to be effective in some patients with C3Nef-positive C3 glomerulopathy 5
• Identification of underlying conditions, such as monoclonal gammopathy, which may impact treatment choices 6
• Serial renal biopsies to study the disease's evolution in response to treatment 6

Treatment Options

Some treatment options that have shown promise in patients with C3 glomerulopathy include:

• Eculizumab, a C5 complement inhibitor, which may be effective in a subset of patients 4
• Daratumumab, an anti-CD38 therapy, which has shown promising results in patients with C3G associated with monoclonal gammopathy 6
• Plasma therapy and immunosuppression, which may be effective in patients with C3Nef-positive C3 glomerulopathy 5
• ACEI, which may be effective in some patients, especially in the early stage of disease 3

Important Considerations

When managing patients with C3 glomerulopathy, it is essential to:

• Characterize the specific form of the disease and identify underlying conditions 6, 2
• Monitor the patient's response to treatment and adjust the treatment plan accordingly 4, 5, 6
• Consider the risk of end-stage renal disease and recurrence after renal transplant 2